Homogeneous catalytic asymmetric hydrogenation is an important reaction for providing chiral intermediates for pharmaceutical agents and other products useful in the life sciences, required in the necessary single stereoisomeric form. In the ongoing quest to design more selective and more efficacious pharmaceutical agents, added structural complexity means that when an asymmetric hydrogenation approach to such agents is contemplated, the existing catalysts may not provide manufacturing solutions in every case and hence design of novel catalysts continues to be an important endeavour.
The majority of known catalysts for asymmetric hydrogenation take the form of transition metal complexes of chiral phosphorus-containing ligands, which are either monodentate or more commonly bidentate. Diphosphines represent the most widely investigated and industrially significant class of such bidentate ligands and a very large number of these ligands are reported in the literature [W. Tang and X. Zhang, Chem. Rev. 2003, 103, 3029-3069; I. C. Lennon and P. H. Moran, Curr. Opin. Drug Discovery Dev. 2003, 6, 855-875]. Bisphospholanes represent a subclass of diphosphines that has proved especially useful in pharmaceutical applications [I. C. Lennon and C. J. Pilkington, Synthesis, 2003, 1639-1642; M. J. Burk, Acc. Chem. Res. 2000, 33, 363-372]. Since the introduction of the pioneering DuPhos family of bisphospholanes, as represented by general formula (A),
numerous alternative bisphospholanes have been reported, based on the following structural variations:                (a) Different backbone structures to 1,2-diphenylene linking the phosphine groups. Ligands of formulae (B) to (D) are representative examples [M. J. Burk, J. E. Feaster, W. A. Nugent and R. L. Harlow, J. Am. Chem. Soc. 1993, 115, 10125-10138; M. J. Burk and M. F. Gross, Tetrahedron Letters, 1994, 35, 9363-9366; J. Holz, A. Monsees, H. Jiao, J. You, I. V. Komarov, C. Fischer, K. Drauz and A. Borner, J. Org. Chem. 2003, 68, 1701-1707].        
                (b) Introduction of extra substituents at the 3-position and/or 4-position of each phospholane ring. The ligand of formula (E) is a representative example [W. Li, Z. Zhang, D. Xiao, X. Zhang J. Org. Chem. 2000, 65, 3489-3496; J. Holz, M. Quirmbach, U. Schmidt, D. Heller, R. Stümer and A. Borner, J. Org. Chem. 1998, 63, 8031-8034; Q. Dai; C-J. Wang, X. Zhang, Tetrahedron 2006, 62, 868-871].        
                (c) The 2-position of each phospholane ring has an alkyl substituent but the 5-position is unsubstituted. This renders such ligands chiral by virtue of the phosphorus atom becoming a chiral centre and accordingly such ligands have been described as “P-chirogenic”. The ligand of formula (F) is a representative example [G. Hoge, J. Am. Chem. Soc. 2004, 126, 9920-9921].        
                (d) The alkyl substituents at the 2- and 5-positions of each phospholane rings are replaced by aryl substituents. To date, the only ligand reported with this structural variation and characterised for catalysis of asymmetric hydrogenation is Ph-BPE (G) (C. J. Pilkington and A. Zanotti-Gerosa, Org. Lett. 2003, 5, 1273-1275).        

General synthetic methods first introduced for the DuPhos family of ligands and applicable to make ligands of types (a)-(c) are not applicable to ligands of type (d) so access to the latter presents technical challenges. For the first time, the present invention serves to significantly broaden the structural diversity of ligands of type (d), leading to enhanced diversity in the catalyst performance (as characterised by substrate scope, enantioselectivity and activity) of the corresponding transition metal complexes.